The principal objective of this proposal is to elucidate the effect of cytomegalovirus infections of embryonic development using the mouse as the model system. This objective will be accomplished by (1) infecting preimplantation embryos in vitro with mouse cytomegalovirus (MCMV); the stages at which the cultured embryos are susceptible to infection will be determined and examined with available techniques. (2) Infecting preimplantation mouse embryos with MCMV in vitro and transferring embryos to surrogate mothers; pathology caused to the fetuses will be studied with histological techniques. Any MCMV genome in the fetal organs will be detected by nucleic acid hybridization techniques. (3) Microinjecting preimplantation mouse embryos with MCMV or MCMV DNA and culturing them to the blastocyst stage; detection of any viral particles, viral replication and viral products will be accomplished by electron microscopy, fluorescent antibody and in situ DNA-RNA cytohybridization techniques. Attempts will also be made to detect MCMV DNA sequences in adult animals derived from such embryos which have been transfered into foster mothers and allowed to come to term. (4) Studying the role played by the endometrium as a possible site for MCMV just prior to blastocyst implantation and the effects of this virus on both the implanted embryos and the endometrium will be determined. These approaches should shed light on the mechanism(s) of congenital abnormalities caused by CMV infection, provide information as to when embryos are susceptible to the infection, and help to elucidate whether the viral infections that occur during implantation could be one of the reasons for miscarriage or maternal waste.